Hyperbaric oxygen therapy as an adjunctive treatment for COVID-19-associated mucormycosis: a report of two cases. / Oxigenoterapia hiperbárica como tratamiento complementario en mucormicosis asociada con la COVID-19: a propósito de dos casos.

OBJECTIVE.: We present the first two cases reported in Peru of the use of adjuvant hyperbaric oxygen therapy (HBOT) in patients with COVID-19-associated mucormycosis (CAM). The first case is a 41-year-old woman, with pain in the left side of the face and palatine region with purulent rhinorrhea for a month. Only an oroantral fistula was found during physical examination. The second case is a 35-year-old male, with decreased left visual acuity and palatal pain with a fistula, draining purulent secretion for four months. Both patients have history of diabetes, had moderate COVID-19 four months prior to admission, and received corticosteroid therapy for this diagnosis. Tomographic evaluation of both patients showed involvement of the maxillary sinus and surrounding bone tissue; both received diagnostic and therapeutic nasal endoscopy for debridement. Histological analysis showed that the samples were compatible with mucormycosis. The patients underwent debridement and were treated with amphotericin B deoxycholate; however, they presented torpid evolution. Then, HBOT was added and the patients showed an evident improvement after four weeks of treatment with subsequent controls without the presence of mucormycosis. We highlight the favorable evolution of these patients while receiving HBOT as treatment for a disease with high morbimortality, which emerged during the pandemic.

Oxigenoterapia hiperbárica como tratamiento complementario en mucormicosis asociada a COVID-19: a propósito de dos casos / Hyperbaric oxygen therapy as an adjunctive treatment for COVID-19-associated mucormycosis: a report of two cases

Reportamos los dos primeros casos, en Perú, sobre el uso del tratamiento con oxigeno hiperbárico coadyuvante (TOHC) en pacientes con mucormicosis asociado a COVID-19 (MAC). El primer caso es una mujer de 41 años, con dolor en hemicara y región palatina izquierdas con rinorrea purulenta de un mes de evolución. Al examen físico, solo evidencia fístula oroantral. El segundo caso se trata de un varón de 35 años, con disminución de agudeza visual izquierda y dolor palatino con fístula que drena secreción purulenta de cuatro meses de evolución. Ambos pacientes tienen el antecedente de diabetes, tuvieron COVID-19 moderado cuatro meses antes del ingreso, y recibieron corticoterapia por este diagnóstico. Ambos pacientes tuvieron una evaluación tomográfica que mostró compromiso del seno maxilar y tejido óseo circundante, con endoscopia nasal diagnóstica y terapéutica para desbridamiento. Se obtuvieron muestras compatibles con mucormicosis en estudio histológico. Los pacientes fueron tratados con limpieza quirúrgica y anfotericina B desoxicolato, sin embargo, presentaron evoluciones tórpidas. Por lo tanto, se adicionó la TOHC y mostraron una mejoría evidente tras cuatro semanas de tratamiento con controles subsiguientes sin presencia de mucormicosis. Resaltamos la evolución de estos pacientes con TOHC, en una enfermedad con importante morbimortalidad, que ha sido emergente durante la pandemia.

We present the first two cases reported in Peru of the use of adjuvant hyperbaric oxygen therapy (HBOT) in patients with COVID-19-associated mucormycosis (CAM). The first case is a 41-year-old woman, with pain in the left side of the face and palatine region with purulent rhinorrhea for a month. Only an oroantral fistula was found during physical examination. The second case is a 35-year-old male, with decreased left visual acuity and palatal pain with a fistula, draining purulent secretion for four months. Both patients have history of diabetes, had moderate COVID-19 four months prior to admission, and received corticosteroid therapy for this diagnosis. Tomographic evaluation of both patients showed involvement of the maxillary sinus and surrounding bone tissue; both received diagnostic and therapeutic nasal endoscopy for debridement. Histological analysis showed that the samples were compatible with mucormycosis. The patients underwent debridement and were treated with amphotericin B deoxycholate; however, they presented torpid evolution. Then, HBOT was added and the patients showed an evident improvement after four weeks of treatment with subsequent controls without the presence of mucormycosis. We highlight the favorable evolution of these patients while receiving HBOT as treatment for a disease with high morbimortality, which emerged during the pandemic.

Metoprolol in Critically Ill Patients With COVID-19.

BACKGROUND: Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. OBJECTIVES: The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS. METHODS: A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. RESULTS: Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). CONCLUSIONS: In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.

Development and validation of a predictive model of in-hospital mortality in COVID-19 patients.

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.

BACKGROUND: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. METHODS: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. FINDINGS: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. INTERPRETATION: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. FUNDING: None.

Tromboembolia pulmonar en la COVID-19. Cuando nada es lo que parece / Pulmonary embolism in COVID-19. When nothing is what it seems

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Hairy cell leukemia treated initially with purine analogs: a retrospective study of 107 patients from the Spanish Cooperative Group on Chronic Lymphocytic Leukemia (GELLC).

Abstract Purine analogs are highly effective in hairy cell leukemia (HCL) with response rates of 85%, but with many late relapses. We have retrospectively reviewed the clinical data from 107 patients treated with pentostatin (n = 27) or cladribine (n = 80), to investigate the long-term efficacy and to identify factors associated with the treatment-free interval (TFI). Complete remission and minimal residual disease (MRD) rates were similar in both groups. Median TFI was shorter (95 vs. 144 months) in the pentostatin group, although the difference was not significant (p = 0.476). MRD+ patients had shorter TFI than MRD- patients (97 months vs. not reached, p < 0.049). A hemoglobin level < 10 g/dL predicted for a shorter TFI only in the pentostatin group. Quality of response and number of hairy cells in the bone marrow are independent risk factors of treatment failure. The relationship between MRD+ and shorter TFI makes it of special interest to explore consolidation therapy with monoclonal antibodies to achieve durable responses.

Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in combination with glimepiride.

BACKGROUND: Type 2 diabetes (T2DM) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs (OADs). Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia. This study compared the efficacy and safety of insulin glargine and NPH insulin, both in combination with a once-daily fixed dose of glimepiride, in terms of glycemic control and incidence of hypoglycemia. METHODS: In this open-label, 24-week randomized trial in ten Latin American countries, T2DM patients poorly controlled on OADs (HbA1c > or = 7.5 and < or = 10.5%) received glimepiride plus insulin glargine (n = 231) or NPH insulin (n = 250) using a forced titration algorithm. The primary endpoint was the equivalence of 24-week mean changes in HbA1c. RESULTS: Insulin glargine and NPH insulin achieved similar HbA1c reductions (adjusted mean difference -0.047; 90% CI -0.232, 0.138; per-protocol analysis). Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin (16.9 vs. 30.0%; p <0.01; safety analysis). Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0% without hypoglycemia (27 vs. 17%; p = 0.014; per-protocol analysis). There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin (p <0.02; full analysis). The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH (1.8 vs. 3.3%; full analysis). CONCLUSIONS: In patients with T2DM, inadequately controlled on OADs, once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin.